Patients with diseases of the thyroid or pituitary gland have abnormalities in the biosynthesis, secretion, and regulation of TSH and its subunits. The proposed studies in this application will investigate the molecular events in the biosynthesis of TSH and its subunits. TSH is one of a family of glycoprotein hormones that consists of two non-covalently linked, dissimilar subunits, designated alpha and beta. We propose to investigate the cellular events that take place in the biosynthesis of TSH. We wish to determine how these processes are regulated, how they may be interdependent, and how they may be involved in intracellular transport, packaging, and secretion of hormone. The isolation of mRNA coding for the TSH subunits and the production of cDNA to mRNA will also study of the translation and transcriptional process. With this background, detailed studies and substantive information will be derived on the regulation of those mechanisms responsible to TSH and subunit biosynthesis. Our initial studies on regulation will be performed on normal bovine anterior pituitaries placed in monolayer culture and then compared withh similar studies using the neoplastic mouse thyrotropic tumor. Our human studis will determine and quantitate the metabolic consequences of vaying degrees of disordered thyroid function particularly as they relate to cardiovascular and pituitary function. In addition, we will expand our investigation of pituitary tumors to assess the efficacy of TSH and subunit measurements for the diagnosis and care of these patients. Unbalanced or discordant alpha and TSH-beta subunits will be carefully quantitated to determine differences in the biosynthesis of glycoprotein subunit in normal and neoplastic tissues.